Michigan Alzheimer's Disease Research Center. This is the resubmission of a competing continuation application to initiate three new scientific projects, continue a pilot grants program, and support multiple scientific investigations of the dementias funded through additional NIH grants utilizing five cores, Administrative, Clinical, Data Management and Statistics, Neuropathology, and Education and Information. The projects investigate Alzheimer's disease (AD), and two focus on MCI and early dementia. Project 1 examines mechanisms underlying the inhibitory effects of XI1 alpha upon cleavage of amyloid precursor protein utilizing transgenic and knockout mice and probes the genetic linkage of XI1 alpha to chromosome 9. Project 2 determines whether PET with [18F]FDG can predict the rate of progression of dementia in MCI and early dementia. Project 3 evaluates the efficacy of PET with [11C]DTBZ in predicting the evolution of early dementia into clinically distinguished AD, dementia with Lewy bodies, and frontotemporal dementia. A minority satellite diagnostic and treatment center will continue to recruit underrepresented urban, predominantly African American, patients to research studies. The approaches utilize major strengths in neurology and neuroscience at the University of Michigan, including the availability of large numbers of normal aged subjects, patients with MCI and with AD, longitudinal studies with autopsy verification, biostatistics, PET, molecular biology, and molecular pharmacology. The MADRC interacts with multiple components of the University for its scientific and educational objectives, particularly the Schools of Medicine, Public Health, and Nursing;Institute for Social Research;Claude Pepper Center, Nathan Shock Center, Institute of Gerontology, and Geriatric Research Education and Clinical Center at the Ann Arbor Veterans Affairs Medical Center. It collaborates with other ADCs on research projects and with NACC in data sharing. It plays a leadership role in statewide dementia initiatives and works closely with national and local chapters of the Alzheimer Association. It provides a rich environment for attracting fellows, junior and senior scientists into cutting-edge basic and clinical research.